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Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension
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SYSNO ASEP 0489812 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Two pharmacological epoxyeicosatrienoic acid-enhancing therapies are effectively antihypertensive and reduce the severity of ischemic arrhythmias in rats with angiotensin II-dependent hypertension Author(s) Červenka, L. (CZ)
Husková, Z. (CZ)
Kopkan, L. (CZ)
Kikerlová, S. (CZ)
Sedláková, L. (CZ)
Vaňourková, Z. (CZ)
Alánová, Petra (FGU-C) RID, ORCID
Kolář, František (FGU-C) RID, ORCID, SAI
Hammock, B.D. (US)
Hwang, S.H. (US)
Imig, J. D. (US)
Falck, J. R. (US)
Sadowski, J. (PL)
Kompanowska - Jezierska, E. (PL)
Neckář, Jan (FGU-C) RID, ORCIDSource Title Journal of Hypertension. - : Lippincott Williams & Wilkins - ISSN 0263-6352
Roč. 36, č. 6 (2018), s. 1326-1341Number of pages 16 s. Language eng - English Country GB - United Kingdom Keywords epoxyeicosatrienoic acid analogue ; epoxyeicosatrienoic acid ; infarct size ; ischemic arrhythmia ; kidney ; renin–angiotensin system ; soluble epoxide hydrolase inhibitor Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GA15-07544S GA ČR - Czech Science Foundation (CSF) Institutional support FGU-C - RVO:67985823 UT WOS 000431515500016 EID SCOPUS 85046619324 DOI 10.1097/HJH.0000000000001708 Annotation We examined the effects of treatment with soluble epoxide hydrolase inhibitor (sEHi) and epoxyeicosatrienoic acids (EETs) analogue (EET-A), given alone or combined, on blood pressure (BP) and ischemia/reperfusion myocardial injury in rats with angiotensin II (ANG II)-dependent hypertension.Ren-2 transgenic rats (TGR) were used as a model of ANG II-dependent hypertension and Hannover Sprague–Dawley rats served as controls. Rats were treated for 14 days with sEHi or EET-A and BP was measured by radiotelemetry. Albuminuria, cardiac hypertrophy and concentrations of ANG II and EETs were determined. Separate groups were subjected to acute myocardial ischemia/reperfusion injury and the infarct size and ventricular arrhythmias were determined.Treatment of TGR with sEHi and EET-A, given alone or combined, decreased BP to a similar degree, reduced albuminuria and cardiac hypertrophy to similar extent, only treatment regimens including sEHi increased myocardial and renal tissue concentrations of EETs. sEHi and EET-A, given alone or combined, suppressed kidney ANG II levels in TGR. Remarkably, infarct size did not significantly differ between TGR and Hannover Sprague–Dawley rats, but the incidence of ischemia-induced ventricular fibrillations was higher in TGR. Application of sEHi and EET-A given alone and combined sEHi and EET-A treatment were all equally effective in reducing life-threatening ventricular fibrillation in TGR.The findings indicate that chronic treatment with either sEHi or EET-A exerts distinct antihypertensive and antiarrhythmic actions in our ANG II-dependent model of hypertension whereas combined administration of sEHi and EET-A does not provide additive antihypertensive or cardioprotective effects. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2019
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